Scale-Up Of Autologous Cell Therapies Realized Through Technological Collaboration
By Trisha Gladd, Editor, Life Science Connect
Since the approval of Genzyme’s Carticel® in 1997, the approval history of the autologous cell therapy market has been a bumpy one. More recently though, the number of autologous cell therapy treatments demonstrating success in clinical trials has grown, making it a market that is now exploding with opportunity.
With allogenic cell therapy manufacturing, a company is producing the same type of cell for all patients from a limited set of approved donors. The product can be scaled up in a dedicated facility and the manufacturer benefits from the volume effects. The cost structure can also be controlled. In the case of autologous cell therapies, the same overall effort is applied, yet the final product is produced for only the patient from which the cells were originally extracted. The process takes 2-3 weeks and requires a substantial amount of manual handling. This creates challenges with not just quality and cost but also training requirements and personnel.
It is this dilemma that forced Dr. Uwe Gottschalk, chief scientific officer at Lonza Group, and his team to evaluate their options in the autologous cell therapy market last year. “We did not want to walk away from an area that holds so much hope but had to conclude that it was extremely challenging to produce these individual, personalized doses at competitive costs,” says Dr. Gottschalk. “This was, of course, very bad news. Not only for companies pursuing an autologous strategy but especially also for the patients who are desperate for these promising therapies.”
At the time when he and his team were “on their way out” of the autologous cell therapy market, an International Stem Cell Conference (2014) was underway. It was at this event where a connection was made between Dr. Behzad Mahdavi, VP of strategic innovation at Lonza and Dr. Nuala Trainor, director of biological programs at Octane Biotech, a medical technology company specializing in solutions for the development and manufacturing of regenerative medicine. “We started an interaction that grew over a period of a year, where we were able to talk about joint interests and spent quite a bit of time talking about the challenges in the industry that each group was focused on,” explains Dr. Timothy Smith, CEO and co-founder of Octane. “Senior management in both organizations worked together to understand the long-term business and strategic interests in terms of company growth.”
The result of this collaboration was announced earlier this summer when the two companies entered into an exclusive technology evaluation of Octane Cocoon, which enables full automation of cell production, from the starting cell population from a single patient all the way to the completion of the cell or tissue product in its final container. “This platform—basically a GMP-process in a box—allows you to kill a number of birds with one stone,” says Dr. Gottschalk. “That’s why we believe it is a game changer.”
Making Commercialization Possible
The automated process of the Cocoon is one of few steps. Once the patient cells are loaded into a “cassette,” the standard biological timeline begins. The entire process is run under automated and controlled conditions inside the cassette, which gives the user the ability to take proactive measures if the donor cells are not doing well. “Everything is set up in a clean environment, but it can run in a lower class production area,” adds Dr. Smith. “This allows for the facility to be far more economical.” There is also potential for significant cost savings due to less manual handling, as this translates into lower labor rates.
The most important factor in all of this is that this technology gives Lonza the solution for a scaled-out production that makes personalized treatments accessible to those who need them. It comes in what is called a “Cocoon Tree,” which is eight Cocoons located on a vertical carousel. The operator can index the Cocoon to whichever position is necessary to remove the cassette and the Cocoon Trees are then installed in a room, where there could potentially be hundreds of Cocoons in operation at the same time.
This enables the cell growth to be completed by a small, automated system instead of a dedicated facility, and the highly-skilled personnel who would normally be assigned to overseeing the production of a treatment for single patients are now able to multiply their efforts and produce hundreds of doses at a time. “That is why this difference is so important,” says Dr. Gottschalk. “It goes beyond optimizing from a ‘version A’ to a ‘version B’, it is about answering the fundamental question as to whether or not a sustainable process is possible.”
The ability of the technology to create this type of industrialized environment is why both Dr. Gottschalk and Dr. Smith believe it could ultimately pave the way for commercial manufacturing of patient-directed therapies.
A Game Changer
The ability to commercialize autologous cell therapies would clearly be a huge step for manufacturers, but more importantly, it would also be a major breakthrough for the pharmaceutical industry and the patients it serves. There are some very promising treatment options with autologous cell therapy, but without a feasible way to make and sell these ”living” drugs or to get them approved by regulatory authorities, the hurdle is almost too high.
In the current system, companies struggle to get a return on their investments and they may not even go down the path of investing in the cell therapy market, as long as appropriate solutions do not exist. For the first time, certain drugs could become available because they can be manufactured under conditions that are economically viable. “Fundamentally, you’re enabling drugs that would otherwise not be possible, and you’re also enabling production in environments that are going to support faster clinical translations,” explains Dr. Smith. “Clinical data is only going to be successful in terms of clinical adoption if the pricing of that product is going to be acceptable to the reimbursement groups.” In other words, while the pharmaceutical industry is in the business of saving lives, it is still, in fact, just that—a business. A pharmaceutical company has to make enough profit to get a return on their investments, as well as those of their stakeholders and investors.
As far as FDA approval goes, Dr. Smith says the Cocoon platform is not a medical device; it is used to produce a medical product and so the supporting data that is going to be necessary for submissions is something Octane can assist clients with. “Each cell-based drug that is approved has to go through a regulatory process for the product. Our system becomes part of the manufacturing process, so we are generating Master File information clients can use for submission with the different regulatory agencies.” Dr. Gottschalk says Lonza has evaluated other technical solutions, but Octane’s has been the most favorable. And although there is still further evaluation to be completed on it, he is confident the company will move forward with implementing this technology into their organization and its services as well as the supply chains of modern patient-specific cell and gene therapies.
The timing of this collaboration bodes well for both companies as the cell therapy market gains tremendous momentum, with a large number of clinical trials currently going through Phase 3. As we see continued success in both clinical trials and technological advancements, both Drs. Gottschalk and Smith expect this to translate into a higher confidence in the cell therapy field, as both an applicable medical treatment as well as a viable investment strategy for growth.